内科学
炎症
溃疡性结肠炎
免疫系统
克罗恩病
结肠炎
作者
Vanessa Zaiatz Bittencourt,Fiona Jones,Miriam Tosetto,Glen A. Doherty,Elizabeth J. Ryan
出处
期刊:Journal of Crohns & Colitis
日期:2021-01-18
卷期号:15 (8): 1316-1325
被引量:4
标识
DOI:10.1093/ecco-jcc/jjab014
摘要
Background and aims Inflammatory Bowel Disease (IBD), comprising Crohn's disease (CD) and ulcerative colitis (UC) are chronic conditions characterized by severe dysregulation of innate and adaptive immunity resulting in the destruction of the intestinal mucosa. Natural Killer (NK) cells play a pivotal role in the dynamic interaction between the innate and adaptive immune response. There is an increasing appreciation for the key role immunometabolism plays in the regulation of NK cell function, yet little remains known about the metabolic profile, cytokine secretion and killing capacity of human NK cells during active IBD. Methods PBMC were isolated from peripheral blood of patients with moderate to severely active IBD and healthy controls. NK cells were stained with a combination of cell surface receptors, intracellular cytokines, proteins and analyzed by flow cytometry. For measurements of NK cell cytotoxicity, the calcein-AM release assay was performed. Metabolic profile was analyzed by extracellular flux analyzer. Results NK cells from IBD patients produce large quantities of pro-inflammatory cytokines, IL-17A and TNF-α ex vivo but have limited killing capability. Furthermore, patient NK cells have reduced mitochondrial mass and oxidative phosphorylation. mTORC1, an important cell and metabolic regulator, demonstrated limited activity in both freshly isolated cells and cytokine stimulated cells. Conclusions Our results demonstrate that circulating NK cells of IBD patients have an unbalanced metabolic profile, with faulty mitochondria and reduced capacity to kill. These aberrations in NK cell metabolism may contribute to defective killing and thus the secondary infections and increased risk of cancer observed in IBD patients.
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